TOBACCO-SMOKE INDUCES BOTH APOPTOSIS AND NECROSIS IN MAMMALIAN-CELLS - DIFFERENTIAL-EFFECTS OF HSP70

Tobacco smoke (TS) has been implicated as a major risk factor in human pulmonary diseases including cancer. In this study, we used TS as a m odel of oxidative stress. TS-mediated oxidative stress has been shown to induce protein oxidation, DNA damage, and cell death. Here we inves tigated, in human and rodent cell lines, whether TS induces cell death by apoptosis or by necrosis. As described for classic oxidants, TS in duced apoptosis at low concentrations and necrosis at higher concentra tions. We have previously described the induction of heat shock (HS) p rotein (HSP) (in particular, HSP70) in human monocytes exposed to TS. HSP70 is implicated in the regulation of cell injury and cell death an d, in particular, modulates apoptosis, as does the antiapoptotic oncop rotein Bcl-2. At both apoptotic and necrotic concentrations, TS induce d a dose-dependent HSP70 expression, whereas Bcl-2 was induced only at necrotic concentrations. TS- or MS-induced HSP had no protective effe cts either on apoptosis or on necrosis, but HSP70 overexpression preve nted TS-induced necrosis and consequently led to increased apoptosis. These results might reconcile the apparently contradictory data previo usly reported on the effects of HSP on apoptosis.